Differential involvement of nucleus tractus solitarius projections and locus coeruleus projections to the basolateral amygdala in morphine-associated memory destabilization

Drug-related memory can be transiently destabilized by memory retrieval, after which memories are reconsolidated. Neurons in the basolateral amygdala (BLA) that are activated by emotional information may be one of the key mechanisms underlying this destabilization. However, the specific neural circuits underlying this destabilization process remain unknown. Because BLA receives noradrenergic inputs from the nucleus tractus solitarius (NTS) and locus coeruleus (LC), we studied the role of afferent projections into the BLA in the destabilization of morphine self-administration memory in rats. We first showed that morphine (unconditioned stimulus, US) + morphine-associated conditioned stimuli (CS) exposure, rather than CS exposure alone, destabilized morphine self-administration memory. Then, we measured projection-specific activation after the US + CS or CS retrieval test using c-fos (activity marker)-labeling in projection areas. Compared with CS exposure, we found that US + CS exposure induced more neuronal activation in the BLA and NTS but not in the LC. Next, we determined the effects of chemogenetic inactivation or activation of NTS or LC projections to BLA (NTS → BLA or LC → BLA) on this destabilization. We found that NTS → BLA, but not LC → BLA inactivation during memory retrieval, prevented memory destabilization induced by US + CS exposure. Furthermore, NTS → BLA, but not LC → BLA activation during CS retrieval induced destabilization. Thus, our results identify a specific neural circuit underlying the transformation of a stable opiate-associated memory into an unstable memory and subsequently guide reconsolidation.